Aloe is a cactus-like plant that grows in hot, dry climates. In the United States, aloe is cultivated in Florida, Texas, and Arizona (90122). Aloe is in a plant family with over 360 species (12164). Materials derived from aloe are used commonly in cosmetics and as medicine (90122).

LIKELY SAFE ...when aloe gel is used topically and appropriately. Aloe gel-containing formulations have been safely applied in clinical trials (101,11982,12096,12098,12159,12160,12163,12164,17418)(90123,90124,90127,90128,90129,90131,97320,98816,103305). When included in topical cosmetics, the Cosmetic Ingredient Review Expert Panel concluded that aloe-derived anthraquinone levels should not exceed 50 ppm (90122).

POSSIBLY SAFE ...when aloe gel is used orally and appropriately, short-term. Aloe gel has been safely used in a dose of 15 mL daily for up to 42 days or 100 mL of a 50% solution twice daily for up to 4 weeks (11984,12164). Also, a specific aloe gel complex (Aloe QDM complex, Univera Inc.) has been safely used at a dose of approximately 600 mg daily for up to 8 weeks (90121). ...when aloe extract is used orally and appropriately, short-term. Aloe extract has been used with apparent safety in a dose of 500 mg daily for one month (101579). Also, an aloe extract enriched in aloe sterols has been used with apparent safety in a dose of 500 mg daily for 12 weeks (101577).

POSSIBLY UNSAFE ...when aloe latex is used orally. There is some evidence that anthraquinones in aloe latex are carcinogenic or promote tumor growth, although data are conflicting (6138,16387,16388,91596,91597). In 2002, the US FDA banned the use of aloe latex in laxative products due to the lack of safety data (8229). ...when aloe whole-leaf extract is used orally. Aloe whole-leaf extract that has not been filtered over charcoal still contains anthraquinones. This type of aloe whole-leaf extract is referred to as being "nondecolorized". The International Agency for Research on Cancer has classified this type of aloe whole-leaf extract as a possible human carcinogen (91598,91908). Although filtering aloe whole-leaf extract over charcoal removes the anthraquinones, some animal research suggests that this filtered extract, which is referred to as being "decolorized", may still cause gene mutations (91598). This suggests that constituents besides anthraquinones may be responsible for the carcinogenicity of aloe whole-leaf extract. It should be noted that commercial products that contain aloe whole-leaf extract may be labeled as containing "whole leaf Aloe vera juice" or "aloe juice" (91908).

LIKELY UNSAFE ...when aloe latex is used orally in high doses. Ingesting aloe latex 1 gram daily for several days can cause nephritis, acute kidney failure, and death (8,8961).

CHILDREN: POSSIBLY SAFE ...when aloe gel is used topically and appropriately. Aloe gel-containing formulations have been safely applied in clinical trials (90124,90131). POSSIBLY UNSAFE ...when aloe latex and aloe whole leaf extracts are used orally in children. Children younger than 12 years may experience abdominal pain, cramps, and diarrhea (4).

PREGNANCY: POSSIBLY UNSAFE ...when used orally. Anthraquinones present in aloe latex and aloe whole leaf extracts have irritant, cathartic, and possible mutagenic effects (4,16387,16388,90122). There are also anecdotal reports and evidence from animal research that anthraquinones or aloe whole leaf extracts might induce abortion and stimulate menstruation; avoid using (4,8,19,90122).

LACTATION: POSSIBLY UNSAFE ...when aloe preparations are used orally. Cathartic and mutagenic anthraquinones present in aloe latex and aloe whole leaf extracts might pass into milk; avoid using (4,19).

•  Dermatologic

  Topically, aloe gel has occasionally been associated with burning (12164,19741,30697,30706), itching (12164,19741,30697), eczema (90122), erythema (19748,30706,90123), contact dermatitis (12163,12164,30695,30736,30737,30738,30740), popular eruption (30732), and urticaria (30712). Also, a case of generalized nummular and popular dermatitis attributed to hypersensitivity has been reported for a 47-year-old male who used aloe leaf gel, both topically and orally, for 4 years (30740).

•  Endocrine

  A case of severe hypokalemia has been reported for a male breast cancer patient who was undergoing chemotherapy and using aloe vera 1 liter daily orally for 2 weeks. The hypokalemia was attributed to the cathartic effects of aloe and resolved once aloe use was discontinued (30704).

•  Gastrointestinal

  Orally, aloe latex can cause abdominal pain and cramps. Long-term use or abuse of aloe latex can cause diarrhea, sometimes with hypokalemia, albuminuria, hematuria, muscle weakness, weight loss, arrhythmia, and pseudomelanosis coli (pigment spots in intestinal mucosa). Pseudomelanosis coli is believed to be harmless, and usually reverses with discontinuation of aloe. It is not directly associated with an increased risk of developing colorectal adenoma or carcinoma (6138). Orally, aloe gel may cause nausea and other gastrointestinal complaints in some patients (104174).
  
  Topically, applying aloe gel in the mouth may cause nausea within 5 minutes of application in some patients (90124).

•  Hematologic

  A case of Henoch-Schonlein purpura, characterized by abdominal pain, purpura, and severe arthralgia, has been reported in a 52-year-old male who drank aloe juice prepared from four to five leaflets for 10 days prior to symptom development (91598).

•  Hepatic

  Cases of acute hepatitis have been reported after ingestion of aloe leaf extracts for between 3 weeks and 5 years. This is thought to be a hypersensitivity reaction (15567,15569,16386,17419,90126,91598). A case of acute hepatitis has also been reported for a 45-year-old female who drank two ounces of Euforia juice (Nuverus International), a product containing green tea, noni, goji, and aloe, daily for one month (90125). However, one small clinical trial in healthy individuals shows that taking aloe gel 2 ounces twice daily for 60 days does not impair liver function (104174).

•  Renal

  Orally, aloe latex can cause hemorrhagic gastritis, nephritis, and acute kidney failure following prolonged use of high doses (1 gram daily or more) (8961).

• Adult

  Oral:

  Various oral formulations of aloe, including aloe extracts, aloe gels, aloe juices, and raw aloe leaves, have been used. Dosing regimens have varied depending on the condition being treated. See Effectiveness section for condition-specific information.
  
  

  Topical:

  Aloe has been used in various topical formulations, including as a gel, cream, vaginal cream, patch, toothpaste, and mouthwash. See Effectiveness section for condition-specific information.

• Children

  Topical:

  Aloe has been used in various topical formulations, including as a gel, cream, mouthwash, and topical solution. See Effectiveness section for condition-specific information.

• Standardization & Formulation

  High-molecular-weight fractions of aloe leaves (AHMs) have been standardized to contain aloin <10 ppm, as well as neutral polysaccharides (molecular weight: 1000 kDa), carbohydrate (90%), and proteins (7%), including glycoprotein (10.7% of protein content) and verectin (82.0% of protein content) (19780).
  
  A specific commercial aloe gel (Aloe Vera Group ApS, Søborg, Denmark) has been standardized to contain 98% aloe leaf gel, with less than 100 ppm of anthraquinones, and the additives xanthan gum, potassium sorbate, sodium benzoate, sodium sulfite, and citric acid (19748).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe gel might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research shows that aloe gel can inhibit platelet aggregation. This inhibition was greater than that seen with celecoxib, but less than that seen with aspirin (105501).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Aloe might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Preliminary clinical research suggests aloe gel might lower blood glucose levels (11983,12164,19756) and have additive effects when used with antidiabetes drugs. Monitor blood glucose levels closely.

DIGOXIN (Lanoxin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, aloe latex might increase the risk of adverse effects when taken with cardiac glycosides.  Details Overuse of aloe latex can increase the risk of adverse effects from cardiac glycoside drugs, such as digoxin, due to potassium depletion. Overuse of aloe, along with cardiac glycoside drugs, can increase the risk of toxicity (19).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe latex might increase the risk of hypokalemia when taken with diuretic drugs.  Details Overuse of aloe latex might compound diuretic-induced potassium loss, increasing the risk of hypokalemia (19).

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe latex might increase the risk for fluid and electrolyte loss when taken with stimulant laxatives.  Details Due to cathartic laxative effects of aloe latex, concomitant use with other stimulant laxatives might compound fluid and electrolyte loss (19,19742,19743,19744).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, aloe latex might increase the risk of bleeding when taken with warfarin.  Details Aloe latex has stimulant laxative effects. In some people aloe latex can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Advise patients who take warfarin not to take excessive amounts of aloe vera.

 Details  Details  Details  Details  Details  Details

 GASTROINTESTINAL (GI) CONDITIONS

 KIDNEY DISORDERS

 PERIOPERATIVE

There is insufficient reliable information available about the presentation or treatment of overdose with aloe.

There is insufficient reliable information available about the pharmacokinetics of aloe.

General: The applicable part of aloe is the leaf. From the leaf, multiple components of aloe can be extracted. Most aloe-containing products use aloe gel or aloe latex. The forms of aloe contain different active constituents and have different pharmacological effects. Aloe gel is the clear, jelly-like substance obtained from the thin-walled mucilaginous cells in the center of the leaf (8224,12164). This form of aloe is often found in topical formulations and in cosmetics. Aloe latex is an intensely bitter, yellow sap or juice produced in the peripheral bundle sheath cells just beneath the leaf skin (12164). It drains from cut leaves and dries to form solid granules, sometimes referred to as "aloes." References to aloe juice or aloe sap are usually describing aloe latex products. Some products contain a homogenized total leaf extract which contains constituents of both the gel and the latex (8224,12164).

Aloe latex contains up to 30% anthraquinones, including glycosides such as barbaloin (aloin), isobarbaloin, and emodin; and free anthraquinones (aglycones) such as aloe-emodin, anthranol, and chrysophanic acid (12164). It also contains resins and aloesin. Aloe gel does not contain the anthraquinones found in aloe latex. Aloe gel contains mono- and poly-saccharides, including acemannan, aloeride, and maloyl glucans; tannins; sterols; enzymes, including cyclooxygenase, amylase, lipase, alkaline phosphatase, and carboxypeptidase; amino acids; saponins; salicylic acid; arachidonic acid; lipids; vitamins; and minerals (4,12164,30686,90122). Sterols in aloe include lophenol, 24-methyl-lophenol, 24-ethyl-lophenol, cycloartenol, and 24-methylene-cycloartanol (101577).

Anti-inflammatory effects: Constituents in aloe may play a role in the reduction of pain and itching associated with inflammation, as shown in laboratory research. In laboratory research, the carboxypeptidase and salicylate components of aloe gel were shown to inhibit bradykinin, a pain-producing agent. Magnesium lactate present can inhibit histamine, which may reduce itching (101). A C-glucosyl chromone component appears to reduce topical inflammation (8223). In colorectal mucosa in vitro, aloe gel has an antioxidant effect, decreasing levels of colorectal prostaglandin E2 and interleukin-8. These effects may explain why aloe gel seems to help some patients with inflammatory bowel disease (12158). Salicylic acid and other antiprostaglandin compounds in aloe may be responsible for aloe's local anti-inflammatory activity, possibly due to an inhibitory effect on the arachidonic acid pathway via cyclooxygenase (30747). In vitro, the maloyl glucan components of aloe also had anti-inflammatory effects (30686).

Antimicrobial effects: Aloe gel seems to have both antibacterial and antifungal properties (101,30692,103306). In animal research, a combination of honey and aloe gel protected against burn wound infection (30707).

Antioxidant effects: The antioxidant effects of aloe may play a role in its anti-inflammatory, antineoplastic, and wound healing effects. Antioxidant effects of aloe pulp have been demonstrated in animal models (30667) and the properties have been attributed to aloesin derivatives and glycoproteins in aloe (30671,30672,30682).

Cancer effects: Preliminary data suggest that anthraquinones may have mutagenic and carcinogenic effects, and may promote tumor growth, although some data are conflicting (6138,16387,16388). Possible mechanisms include intercalation of the tricyclic anthraquinone structure into DNA, inhibition of topoisomerase II, and induction of cell signaling and growth (16387,16388). Also, the constituent aloe-emodin is thought to induce DNA damage through the generation of reactive oxygen species (30684).

However, some evidence suggests that aloe or its constituents may have anticancer effects. In vitro, individual maloyl glucans had antagonistic effects on cell proliferation, with one stimulating and one inhibiting, suggesting a mechanism by which aloe may have both pro-cancer and anti-cancer effects (30686). Antileukemic and antimutagenic effects of aloe have been shown in vitro and attributed to di-(2-ethylhexyl) phthalate (DEHP) (30666). Another constituent, aloe-emodin, has been shown to promote apoptosis by various possible mechanisms, including the involvement of p53 (30673,30685,30688). Also, in vitro, aloe-emodin had anti-angiogenesis effects, possibly by affecting urokinase secretion and tubule formation of endothelial cells (30689). In animal research, aloe itself appears to affect detoxification of reactive metabolites by liver and other organs (30667).

Dental effects: In human research, use of an aloe gel rinse in the mouth reduces counts of salivary Streptococcus mutans, the pathogenic bacteria involved in the formation of dental plaque (103306).

Dermatological effects: Aloe is commonly used as an ingredient in skin care products. In human research, aloe gel has been shown to reduce ultraviolet (UV)-induced erythema (19770) and increase water content of the stratum corneum (19758). Oral intake of aloe vera gel powder has also been shown to increase skin elasticity, skin hydration, and collagen content of the dermis and reduce transepidermal water loss and markers of skin fatigue (95942,101577). When applied to psoriatic plaques, aloe extract cream seems to reduce cellular desquamation, erythema, and infiltration. This results in reduction or resolution of the plaques (12096). In an in vitro model of psoriasis, which used tumor necrosis factor (TNF) alpha to stimulate over-production of cultured human keratinocytes, a polysaccharide extract of aloe mixed into the culture medium in a concentration of 20-80 mcg/mL produced a dose-dependent reduction in keratinocyte proliferation, and a reduction in levels of inflammatory mediators such as interleukins 8 and 12 (98818).

Detoxification effects: There is interest in using aloe to remove toxins from the body. A small clinical study in people who smoke 20 or more cigarettes daily shows that consuming aloe polysaccharide 600 mg daily for 4 weeks increases urinary excretion of tobacco carcinogens and nicotine (102176).

Gastrointestinal effects: Aloe is commonly used for inflammatory bowel diseases and ulcers. In colorectal mucosa in vitro, aloe gel has an antioxidant effect, decreasing levels of colorectal prostaglandin E2 and interleukin-8. These effects may explain why aloe gel seems to help some patients with inflammatory bowel disease (12158).

Hypoglycemic effects: Preliminary animal research suggests that aloe gel might have hypoglycemic effects (11983). Possible mechanisms of action have been explored in laboratory research. Constituents of Kitachi aloe leaf pulp and skin have been found to stimulate beta-cells in diabetic mice, thereby lowering blood glucose levels (30758). However, in human research in patients with diabetes, the evidence is contradictory (12164,17420,17488,17489,19756,90121).

Immune effects: There is interest in using aloe as an immune stimulant. In mice, a mannose-rich polysaccharide fraction of aloe gel has been shown to enhance antibody production (30730). Clinical research in healthy adults shows that taking a specific oral product (ImmunoAloe; Univera Co Ltd) containing processed aloe gel 238 mg as 3 capsules three times daily, starting 4 weeks prior to receiving an inactivated influenza vaccine and continuing for an additional 4 weeks, does not appear to increase seroprotection or seroconversion rates at weeks 4 or 24 after vaccination when compared with placebo (108720).

Laxative effects: Anthraquinones contain a tricyclic anthracene nucleus and are cleaved to form anthrones in the colon which are responsible for potent laxative effects (16). Anthrones irritate mucous membranes, causing increased mucous secretion and peristalsis. They also increase fluid and electrolyte secretion into the lumen, causing a feeling of distention. The cathartic effects occur within 10 hours. Water and electrolyte reabsorption are inhibited (8). Aloe latex causes a loss of potassium from cells paralyzing the intestinal muscles. With continued use, increasing doses are needed for a laxative effect, and electrolyte depletion can occur (4,8).

Radioprotective effects: Some clinical evidence suggests that aloe may prevent mucositis associated with radiation therapy (19767,19964). In vitro, radioprotective effects of aloe polysaccharides were associated with modulation of the cell cycle (30677,30683).

Wound healing effects: Aloe gel might inhibit the synthesis of thromboxane A2, a potent vasoconstrictor and thereby increase microcirculation and prevent ischemia in wounds. This may speed the healing of burns and frostbite (101,8224,12161,12162). In animal models, aloe seems to prevent the inhibition of wound contraction caused by silver sulfadiazine (SSD). SSD is often applied to wounds, especially burn wounds, to prevent infection. But SSD seems to slow wound healing by inhibiting contraction and epithelialization. Applying aloe in conjunction with SSD seems to improve the speed of wound healing compared to SSD alone (12097). However, there is also evidence SSD improves the rate of wound healing better than aloe when each product is used alone (12161). This suggests that there might be a synergistic effect when SSD and aloe are used together. In animal models of frostbite, aloe gel seems to be more effective for improving tissue survival than pentoxifylline. The combination of pentoxifylline plus aloe gel seems to be better than either agent alone (12162). Topical aloe's anti-inflammatory properties do not appear to interfere with wound healing but rather increase wound tensile strength (30741), possibly due to the fibroblast-stimulating activity of mannose-6-phosphate (30742). Polysaccharides such as mannose stimulate the activity of fibroblast growth factor and increase collagen production. Aloe gel also seems to increase collagen crosslinking, accelerating wound healing (98816).

In a study using cultures of human skin fibroblasts and keratinocytes, adding aloe vera gel 2-3% to the culture medium increased proliferation and migration of both types of cells, suggesting the gel could increase the rate of reepithelialization of wounds (98817,110210).